1. Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA
2. EMBL Outstation – Hinxton, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK
3. Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, 65 Landsdowne Street, Cambridge, Massachusetts 02139, USA

Correspondence to: Howard L. Weiner¹ Correspondence and requests for materials should be addressed to H.W. (Email: hweiner@rics.bwh.harvard.edu).

Abstract

Regulatory T cells (T_reg) expressing the transcription factor Foxp3 control the autoreactive components of the immune system. The development of T_reg cells is reciprocally related to that of pro-inflammatory T cells producing interleukin-17 (T_H17). Although T_reg cell dysfunction and/or T_H17 cell dysregulation are thought to contribute to the development of autoimmune disorders, little is known about the physiological pathways that control the generation of these cell lineages. Here we report the identification of the ligand-activated transcription factor aryl hydrocarbon receptor (AHR) as a regulator of T_reg and T_H17 cell differentiation in mice. AHR activation by its ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin induced functional T_reg cells that suppressed experimental autoimmune encephalomyelitis. On the other hand, AHR activation by 6-formylindolo[3,2-b]carbazole interfered with T_reg cell development, boosted T_H17 cell differentiation and increased the severity of experimental autoimmune encephalomyelitis in mice. Thus, AHR regulates both T_reg and T_H17 cell differentiation in a ligand-specific fashion, constituting a unique target for therapeutic immunomodulation.

1. Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA
2. EMBL Outstation – Hinxton, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK
3. Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, 65 Landsdowne Street, Cambridge, Massachusetts 02139, USA

Correspondence to: Howard L. Weiner¹ Correspondence and requests for materials should be addressed to H.W. (Email: hweiner@rics.bwh.harvard.edu).

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